Autism is a devastating and common developmental disorder and a major public health concern. Early detection of autism in high risk infants is critical to these children, their families, and the systems that support them. Fragile X syndrome (FXS) is the leading genetic cause of autism, and both FXS and the FMR1 premutation (FXpm) are highly associated with autism. Despite the high association of autism and FMR1 gene mutations, no study has examined early indicators of autism in FXS or FXpm or examined specificity of early autism indicators in FX to idiopathic (non-FX) autism. This application "Emergence and Stability of Autism in Fragile X Syndrome" proposes a longitudinal prospective study of the early autism features in infants with FXS and FXpm at 9, 12, and 24 in contrast to infants with an older sibling diagnosed with autism (hereafter referred to as "ASIBS") and typical controls (TD). This application takes advantage of recent scientific advances in the identification of autism in the first 2 years of life, characterization of the FXS and FXpm-autism co-morbidity and findings from developmental neuroscience to identify underlying physiological mechanisms associated with early emerging autistic features (e.g., attention). This work will advance our understanding of the progression of autism features during the key risk transition period for two conditions of major health importance: FX and autism. In this project, we will use a combined behavioral, both standardized and laboratory measures, and biomarker approach focused on autistic behavior as a continuum rather than rigid diagnostic categories. PUBLIC HEALTH RELEVANCE: Autism is a Devastating and Common Developmental Disorder that is a Major Public Health Concern. With a prevalence of ~1:110 (1:70 males) and a cost of $35 billion per year, the early detection of autism in high risk infants is critical to these children, their families and the systems that support them.